Minority Predoctoral Fellowship Program

Meharry Medical College, Nashville TN

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Interesting evidence demonstrates that hydrogen peroxide (H2O2) promotes endothelial cell (EC) proliferation when present in low concentrations (Burdon R.H. et al., 1990; Suzuki et al., 1997). However, the mechanisms by which H2O2 regulate EC proliferation have not been fully defined. My preliminary study clearly demonstrated that aortic ECs from mice heterozygously overexpressing human catalase transgene (hCatTg0/+) had a reduced growth rate, an increased doubling time and a delayed G1 phase duration time when compared to the aortic ECs obtained from wild-type mice. Catalase is an antioxidant that converts H2O2 to water and oxygen. Thus, the results from the preliminary study indicate that H2O2 promotes EC proliferation by shortening the cell cycle. It is well known that cyclin dependent kinase (CDKs) play an essential role in mammalian cell cycle progression (Potente et al., 2002; Sherr and Roberts, 1999b; Joyce et al., 2002). The primary goal of this proposal is to test the hypothesis that an increase in the activity of cyclin dependent kinases (CDKs) is a mechanism by which H2O2 accelerates the cell cycle in mouse aortic mouse endothelial cells.